ZNF385B is characteristically expressed in germinal center B cells and involved in B‐cell apoptosis

We previously identified zinc finger (ZF) protein ZNF385B as a molecule specifically expressed in Burkitt's lymphoma (BL) among hematologic malignancies. Here, we investigated ZNF385B expression in healthy B cells in a variety of hematological tissues by RT‐PCR and immunohistochemistry. ZNF385B...

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Bibliographic Details
Published in:European journal of immunology 2012-12, Vol.42 (12), p.3405-3415
Main Authors: Iijima, Kazutoshi, Yamada, Hiroyuki, Miharu, Masashi, Imadome, Ken‐Ichi, Miyagawa, Yoshitaka, Akimoto, Shingo, Kobayashi, Kenichiro, Okita, Hajime, Nakazawa, Atsuko, Fujiwara, Shigeyoshi, Fujimoto, Junichiro, Kiyokawa, Nobutaka
Format: Article
Language:English
Subjects:
Antigens, CD20 - genetics
Antigens, CD20 - immunology
Apoptosis
Apoptosis - genetics
Apoptosis - immunology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B‐cell development
Cell Line
Cell survival
Cells
DNA repair mechanisms
Female
Gene Deletion
Gene Expression Regulation - genetics
Gene Expression Regulation - immunology
Germinal Center - immunology
Germinal Center - metabolism
Humans
Immune system
Lymphoid organs
Male
Proteins
Transcriptional Activation - genetics
Transcriptional Activation - immunology
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - immunology
Zinc Fingers - genetics
Zinc Fingers - immunology
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Summary:We previously identified zinc finger (ZF) protein ZNF385B as a molecule specifically expressed in Burkitt's lymphoma (BL) among hematologic malignancies. Here, we investigated ZNF385B expression in healthy B cells in a variety of hematological tissues by RT‐PCR and immunohistochemistry. ZNF385B expression was found to be limited to a subset of GC B cells, the healthy counterpart to BL B cells. To elucidate the function of ZNF385B in healthy B cells, we established a tetracycline‐controlled protein‐inducible system in B‐cell lines and observed that ectopic expression of the longest transcript variant of ZNF385B, possessing four ZF domains, induced upregulation of PERP and FAS/CD95, a downstream target of p53, and activation of caspase, resulting in apoptosis induction. However, a ZNF385B deletion mutant with three ZF domains corresponding to shorter isoforms, did not induce upregulation; rather it inhibited apoptosis induced by CD20 cross‐linking and BCR stimulation. The direct binding of ZNF385B with p53 has suggested the involvement of ZNF385B in B‐cell apoptosis via modulation of p53 transactivation; our data indicate that ZNF385B characteristically expressed in GC B cells has both proapoptotic and antiapoptotic activities depending on the type of isoform and should be a novel player in GC B‐cell selection.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201242530